Synthesis and in vitro cytotoxicity evaluation of 4-aminoquinoline derivatives [J]

Tumour Biology Group, Northeastern Ontario Regional Cancer Program at the Sudbury Regional Hospital, 41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada.
Biomedecine [?] Pharmacotherapy (Impact Factor: 2.02). 03/2008; 62(2):65-9. DOI: 10.1016/j.biopha.2007.04.007
Source: PubMed


A series of 4-aminoquinoline derivatives were synthesized by the reaction of 4-chloro-7-substituted-quinolines with the corresponding mono/dialkyl amines. The structures of the synthesized compounds were confirmed by NMR and FAB-MS spectral and elemental analyses. Subsequently, the compounds were examined for their cytotoxic effects on two different human breast tumor cell lines: MCF7 and MDA-MB468. Although all compounds examined were quite effective on both cell lines, the compound N'-(7-chloro-quinolin-4-yl)-N,N-dimethyl-ethane-1,2-diamine emerged as the most active compound of the series. It was particularly potent against MDA-MB 468 cells when compared to chloroquine and amodiaquine. The compound butyl-(7-fluoro-quinolin-4-yl)-amine showed more potent effects on MCF-7 cells when compared to chloroquine. Therefore, 4-aminoquinoline can serve as the prototype molecule for further development of a new class of anticancer agents.

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    • "Chloroquine (7-chloro-4- [4-diethylamino-1-methyl-butylamino] quinoline; CQ) is commonly sold as malaria medication and is used as an anti-inflammation drug for rheumatoid arthritis, discoid lupus erythematosus, and amoebic hepatitis[17],[18]. In 1992, Djordevic et al.[19] reported that treating mouse melanoma cells with CQ potentiated radiation-induced cell killing. "
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    ABSTRACT: Although the anti-malaria drug chloroquine (CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials, the potential mechanisms underlying this enhancement are still unclear. Here, we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan (TPT). The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations. Cell viability was assessed using the MTT assay. The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow cytometry. Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting. The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy. CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion. CQ inhibited TPT-induced autophagy, which modified the cytotoxicity of TPT. However, CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability. This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy, implying that CQ has significant potential as a chemotherapeutic enhancer.
    Full-text · Article · Oct 2011 · Chinese journal of cancer
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    ABSTRACT: A series of novel 4-aminoquinoline derivatives were synthesized as antitumor agents by reacting 4-chloroquinoline with the corresponding mono/dialkyl amines. The cytotoxicity of these compounds was evaluated in vitro against HCT-116, A549, DU-145, HepG2, and LN229 cell lines. The results showed that most of the synthesized compounds displayed excellent cytotoxicity, and 5,7-dimethoxy-2-phenyl-N-propylquinoline-4-amine (6a) displayed the most potent cytotoxicity against HCT-116 cells. Furthermore, 6a could decrease VEGF protein expression. Graphical abstract The synthesis and antitumor activity of 4-aminoquinoline derivatives have been described.
    No preview · Article · Jun 2012 · Medicinal Chemistry Research
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